Post-Authorization Safety Studies of Acute Liver Injury and Severe Complications of Urinary Tract Infection in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting

Heather E. Danysh (), Catherine B. Johannes, Daniel C. Beachler, J. Bradley Layton, Ryan Ziemiecki, Alejandro Arana, Jade Dinh, Ling Li, Brian Calingaert, Manel Pladevall-Vila, Phillip R. Hunt, Hungta Chen, Cecilia Karlsson, Kristina Johnsson and Alicia Gilsenan
Additional contact information
Heather E. Danysh: RTI Health Solutions
Catherine B. Johannes: RTI Health Solutions
Daniel C. Beachler: HealthCore, Inc.
J. Bradley Layton: RTI Health Solutions
Ryan Ziemiecki: RTI Health Solutions
Alejandro Arana: RTI Health Solutions
Jade Dinh: HealthCore, Inc.
Ling Li: HealthCore, Inc.
Brian Calingaert: RTI Health Solutions
Manel Pladevall-Vila: RTI Health Solutions
Phillip R. Hunt: AstraZeneca
Hungta Chen: AstraZeneca
Cecilia Karlsson: AstraZeneca
Kristina Johnsson: AstraZeneca
Alicia Gilsenan: RTI Health Solutions

Drug Safety, 2023, vol. 46, issue 2, No 6, 175-193

Abstract: Abstract Introduction At the time of dapagliflozin’s approval in Europe (2012) to treat patients with type 2 diabetes mellitus, concerns regarding acute liver injury and severe complications of urinary tract infection (sUTI) led to two post-authorization safety (PAS) studies of these outcomes to monitor the safety of dapagliflozin in real-world use. Objective To investigate the incidence of hospitalization for acute liver injury (hALI) or sUTI (pyelonephritis or urosepsis) among patients initiating dapagliflozin compared with other glucose-lowering drugs (GLDs). Methods These two noninterventional cohort studies identified initiators of dapagliflozin and comparator GLDs in November 2012–February 2019 using data from three longitudinal, population-based data sources: Clinical Practice Research Datalink (UK), the HealthCore Integrated Research Database (USA), and the Medicare database (USA). Outcomes (hALI and sUTI) were identified with electronic algorithms. Incidence rates were estimated by exposure group. Incidence rate ratios (IRRs) were calculated comparing dapagliflozin to comparator GLDs, using propensity score trimming and stratification to address confounding. The sUTI analyses were conducted separately by sex. Results In all data sources, hALI and sUTI incidence rates were generally lower in dapagliflozin initiators than comparator GLD initiators. The adjusted IRR (95% confidence interval) pooled across data sources for hALI was 0.85 (0.59–1.24) and for sUTI was 0.76 (0.60–0.96) in females and 0.74 (0.56–1.00) in males. Findings from sensitivity analyses were largely consistent with the primary analyses. Conclusions These real-world studies do not suggest increased risks of hALI or sUTI, and they suggest a potential decreased risk of sUTI with dapagliflozin exposure compared with other GLDs.

Date: 2023
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DOI: 10.1007/s40264-022-01262-4

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